ROLE OF DOUBLE MINUTES AND HSR MARKERS IN TUMOR CELLS

双分钟和 HSR 标记物在肿瘤细胞中的作用

• 批准号: 3172171
• 负责人: DONNA L GEORGE
• 金额: $ 10.02万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-12-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3172171
• 关键词: chromosome complement; cytogenetics; drug resistance; genetic library; genetic manipulation; genetic transcription; heterochromatin; histochemistry /cytochemistry; linkage mapping; messenger RNA; methotrexate; molecular cloning; neoplasm /cancer genetics; neuroblastoma; nucleic acid sequence; tissue /cell culture

We are investigating the structural organization and functional significance in tumor cells of chromosomal anomalies termed (1) homogeneously staining regions (HSRs) and (2) double-minute chromosomes (DMs). We have obtained evidence that DMs and HSRs present in related lines of Y1 mouse adrenocortical tumor cells are similar in molecular composition and result from a process of gene amplification. An analysis of DMs in a transformed derivative of 3T3 mouse cells revealed that DMs in these cells also result from gene amplification, but the amplified sequences are different from those in the Y1 cells. We have demonstrated that cellular sequences related to the transforming gene (oncogene) of the Kirsten sarcoma virus (Ki-ras) are amplified 30-\to 60-fold in the Y1 cells, and the amplified sequences are present on DMs and HSRs. Further, the level of the cellular Ki-ras-specific mRNA and of the protein p21 coded for by this gene are elevated in these cells. Studies in progress should provide information concerning: (1)\the organization of the amplified DNA; (2)\the number of genes amplified; and (3)\the mechanisms by which the amplification and enhanced expression of cellular oncogenes might contribute to the initiation and/or maintenance of neoplastic transformation of some cells. (I)

我们正在调查的结构组织和功能 染色体异常在肿瘤细胞中的意义称为（1） 均匀染色区域（HSRs）和（2）双微体染色体 （DM）。 我们已经获得的证据表明，DM和HSR存在于相关的 Y1小鼠肾上腺皮质肿瘤细胞系在分子水平上相似， 组成和结果的基因扩增的过程。 分析 在3 T3小鼠细胞的转化衍生物中的DMs显示， 这些细胞也是基因扩增的结果，但扩增的 序列与Y1细胞中的序列不同。 我们已经证明 与肿瘤细胞的转化基因（癌基因）相关的细胞序列 Kirsten肉瘤病毒（Ki-ras）在Y1细胞中扩增30- 1至60倍， 细胞，并且扩增的序列存在于DM和HSR上。 此外，本发明还 细胞Ki-ras特异性mRNA和编码p21蛋白的水平 在这些细胞中的表达水平升高。 正在进行的研究应 提供有关以下方面的信息：（1）扩增DNA的组织; (2)扩增基因的数量;（3）扩增基因的机制。 细胞癌基因的扩增和增强表达可能 促进肿瘤的发生和/或维持 一些细胞的转化。 （一）

项目成果

Structural and functional characterization of the promoter region of the mouse c-Ki-ras gene.

小鼠 c-Ki-ras 基因启动子区域的结构和功能表征。

• DOI: 10.1128/mcb.7.7.2592-2596.1987
• 发表时间: 1987
• 期刊: Molecular and cellular biology
• 影响因子: 5.3
• 作者: Hoffman,EK;Trusko,SP;Freeman,N;George,DL
• 通讯作者: George,DL

Structure and expression of amplified cKi-ras gene sequences in Y1 mouse adrenal tumor cells.

Y1 小鼠肾上腺肿瘤细胞中扩增的 cKi-ras 基因序列的结构和表达。

• DOI: 10.1002/j.1460-2075.1985.tb03760.x
• 发表时间: 1985
• 期刊: The EMBO journal
• 作者: George,DL;Scott,AF;Trusko,S;Glick,B;Ford,E;Dorney,DJ
• 通讯作者: Dorney,DJ